Significance Because maternal antibody can neutralize the measles vaccine virus in the infant, it cannot be administered before 6 to 9 months of age. Objectives The goal of this project is to develop a safe and effective vaccine for measles that can be given at birth. Results Newborn rhesus macaques were immunized with vaccinia viruses expressing measles hemagglutinin and fusion proteins, using the WR strain of vaccinia virus or MVA. The infants were boosted at 3 months and challenged intranasally with measles virus at 6 months. Some of the newborn monkeys received measles immune globulin (MIG) prior to the first immunization to mimic maternal antibody and some infants had natural maternal antibody at birth. Vaccination induced high-titer neutralizing antibody only in those infants that did not receive MIG or have maternal antibody. But cytotoxic T cell responses were elicited in monkeys regardless of MIG or maternal antibody. Three levels of protection were observed after measles virus challenge 1) No clinical signs of measles and no virus recovery. This response was observed in infants vaccinated without MIG or maternal antibody, 2) No signs of measles but low-level viremia. This response occurred in infants that had low levels of MIG or ma ternal antibody, 3) Skin rash and viremia similar to control monkeys in those monkeys with high levels of MIG or maternal antibody. The vaccinia MVA strain, further attenuated for safety in humans, was effective in the absence of maternal antibody. Thus vaccinia viruses expressing measles genes were effective in preventing measles in infant monkeys, but these vectors did not protect against systemic infection in the presence of maternal antibody at birth. However, the infection was reduced and disease was prevented. Future Directions Other vectors that can prime strong T cell responses to measles antigens in infant monkeys will be studied. KEY WORDS measles, vaccine, infant health FUNDING CDC Cooperative Agreement CCU913348